Tumors of thyroid gland

1. Benign Tumors

Follicular Adenoma

• Benign proliferation of glandular elements, from follicular epithelium.
• Usually solitary.
• Most are non-functional; a small subset are “toxic adenomas” producing thyroid hormone → thyrotoxicosis.

Morphology

• Solitary, spherical lesion.
• Well-demarcated by intact capsule.
• No capsular or vascular invasion (distinguishes from carcinoma).

Clinical features

• Painless nodule.
• Non-toxic adenomas: take up less iodine → “cold” nodules on radionuclide scan (more likely malignant).
• Toxic adenomas: “hot/warm” nodules → thyrotoxicosis (benign behavior).
• Cold > 50 % chance malignant in some series; hot rarely malignant.
• Evaluation: ultrasonography + fine-needle aspiration biopsy (FNAB).
• Excellent prognosis; don’t recur or metastasize.

2. Malignant Tumors

Overview

• Carcinomas of thyroid are relatively uncommon.
• Usually soft (vs other carcinomas).
• Causes: genetic (familial) + environmental (ionizing radiation — strongest risk).
• Subtypes: papillary, follicular, medullary, anaplastic.

A) Papillary Carcinoma (> 85 %)

• Most common thyroid cancer.
• Any age; ionizing radiation exposure is a strong risk.
• Solitary or multifocal in thyroid.
• Often cystic with fibrosis + calcifications.

Diagnosis (nuclear features)

• “Orphan Annie eye” / “ground-glass” nuclei (finely dispersed chromatin).
• Pseudoinclusions (cytoplasmic invaginations resembling intranuclear inclusions).
• Nuclear grooves.
• Psammoma bodies (concentrically calcified structures).

Clinical

• Non-functional → painless neck mass or cervical LN metastasis.
• Lymphatic spread (cervical LN).
• Tx: thyroidectomy + neighboring LN dissection → very good prognosis (~95 % 10-yr survival).
• BRAF + RET/PTC mutations.

B) Follicular Carcinoma (5–15 %)

• 2nd most common.
• Women, older age than papillary.
• Cause: iodine deficiency → ↑ in iodine-deficient regions.
• Always encapsulated, unilocular.

Diagnosis (vs follicular adenoma)

• Capsular invasion.
• Surrounding parenchymal + vascular invasion.
• (Cannot diagnose by FNA — needs full capsule histology.)

Clinical

• Hematogenous metastasis → lungs, bone, liver.
• Tx: surgical removal of tumor + thyroidectomy.
• RAS, PAX8-PPARγ mutations.

C) Medullary Carcinoma (5 %)

• From parafollicular C cells of thyroid.
• C cells retain ability to secrete calcitonin → diagnostic + tumor marker.
• Sporadic (adults) or familial (MEN-2A/2B → younger patients).
• RET proto-oncogene mutation in both forms.

Morphology

• Solitary nodule or multifocal in both lobes.
• Amyloid deposits in stroma (calcitonin-derived; Congo red positive with apple-green birefringence).
• Familial form: multicentric C-cell hyperplasia.

Clinical

• Cervical LN metastasis; distant rare.
• No hypocalcemia despite ↑ calcitonin (compensation).
• Tx: thyroidectomy (total).
• MEN-2 → screen for pheochromocytoma + parathyroid disease.

D) Anaplastic Carcinoma (< 5 %)

• Most aggressive thyroid malignancy.
• Older patients (~65 yr).
• Causes: from multinodular goiter or differentiated carcinoma (dedifferentiation).
• Histology: highly infiltrative anaplastic cells.
• Death in < 1 yr from aggressive local growth (airway compression).

3. Summary Table

Type	%	Origin	Spread	Key features	Prognosis
Papillary	85 %	Follicular cells	Lymphatic	Orphan Annie nuclei + psammoma bodies + nuclear grooves; radiation; BRAF, RET/PTC	Excellent
Follicular	5–15 %	Follicular cells	Hematogenous (lung, bone, liver)	Encapsulated; capsular + vascular invasion distinguishes from adenoma; iodine deficiency	Good
Medullary	5 %	Parafollicular C cells	LN	Calcitonin • amyloid (Congo red); RET; MEN-2	Variable
Anaplastic	< 5 %	Undifferentiated	Aggressive local	Older patients, dedifferentiated, p53	Very poor (< 1 yr)

💡 High-yield: Follicular adenoma = benign, encapsulated, cold nodule more often malignant; toxic = hot, thyrotoxicosis. Diagnosis = FNAB. Papillary = #1 (>85 %), radiation, Orphan Annie nuclei + psammoma bodies + nuclear grooves + pseudoinclusions, lymphatic, BRAF/RET/PTC, excellent prognosis. Follicular = iodine deficiency, encapsulated, capsular + vascular invasion required for dx, hematogenous to lung/bone/liver. Medullary = C cells, calcitonin + amyloid (Congo red), RET (MEN-2). Anaplastic = old, undifferentiated, death in <1 yr.